Dissecting the tumor ecosystem of liver cancers in the single-cell era

Primary liver cancers (PLCs) are a broad class of malignancies that include HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular and intrahepatic cholangiocarcinoma. PLCs are often associated with a poor prognosis due to their high relapse and low therapeutic response rates. Importantly, PLCs exist within a dynamic and complex tumor ecosystem, which includes malignant, immune, and stromal cells. It is critical to dissect the PLC tumor ecosystem to uncover the underlying mechanisms associated with tumorigenesis, relapse, and treatment resistance to facilitate the discovery of novel therapeutic targets. Single-cell and spatial multi-omics sequencing techniques offer an unprecedented opportunity to elucidate spatiotemporal interactions among heterogeneous cell types within the complex tumor ecosystem. In this review, we describe the latest advances in single-cell and spatial technologies and review their applications with respect to dissecting liver cancer tumor ecosystems.